Abstract:
:To study the role of the BH3 domain in mediating pro-apoptotic and anti-apoptotic activities of Bcl-2 family members, we identified a series of novel small molecules (BH3Is) that inhibit the binding of the Bak BH3 peptide to Bcl-xL. NMR analyses revealed that BH3Is target the BH3-binding pocket of Bcl-xL. Inhibitors specifically block the BH3-domain-mediated heterodimerization between Bcl-2 family members in vitro and in vivo and induce apoptosis. Our results indicate that BH3-dependent heterodimerization is the key function of anti-apoptotic Bcl-2 family members and is required for the maintenance of cellular homeostasis.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Degterev A,Lugovskoy A,Cardone M,Mulley B,Wagner G,Mitchison T,Yuan Jdoi
10.1038/35055085keywords:
subject
Has Abstractpub_date
2001-02-01 00:00:00pages
173-82issue
2eissn
1465-7392issn
1476-4679journal_volume
3pub_type
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